Explore the vast range of titles available.

Objectives. Fatty acids (FA) modulate oxidative stress, reactive oxygen species (ROS) production, and inflammatory processes in spermatogenesis. Methods. The amount of 17 different FAs and the level of F2-isoprostanes (F2-IsoPs) and cytoplasmic phospholipase A2 (cPLA2) were compared and correlated to sperm characteristics; these last ones were evaluated by light and electronic microscopy in varicocele and idiopathic infertile patients. Results. Total n-3 polyunsaturated acids (PUFAs) and docosahexaenoic acid (DHA), one of the n-3 PUFAs, were significantly reduced in idiopathic infertile men compared to controls (P<0.05). In the whole studied population, oleic acid and total monounsaturated acids (MUFAs) correlated negatively with sperm concentration, progressive motility, normal morphology, vitality, and fertility index and positively with sperm necrosis. Eicosapentaenoic acid (EPA) amount was positively correlated with the percentage of sperm necrosis and cPLA2 level and negatively with sperm concentration. Sperm vitality was negatively correlated with the saturated fatty acids (SFAs). In infertile groups, cPLA2 was negatively correlated with DHA and n-3 PUFAs (both P<0.05) and positively with EPA (P<0.05). In the varicocele group, sperm vitality was negatively correlated with palmitoleic acid and total n-6 PUFAs (P<0.05); sperm apoptosis was positively correlated with the total SFA percentage (P<0.05). Conclusions. FA composition in sperm membrane and the metabolism of sperm FAs are interrelated parameters, both relevant in sperm maturation processes and fertility.

The metabolism of polyunsaturated fatty acids (PUFAs) plays an important role in male reproduction. Linoleic and alpha-linolenic acids need to be provided in the diet and they are converted into long chain polyunsaturated fatty acids by steps of elongation and desaturation, exerted by elongases 2 (ELOVL2) and 5 (ELOVL5) and Δ5- (FADS1) and Δ6-desaturase (FADS2). This study aims to assess the gene expression and localization of enzymes involved in the synthesis of n-3 and n-6 long-chain PUFAs in control rabbits and those fed diets containing 10% extruded flaxseed. Enzyme and PUFA localization were assessed in the testes and epididymis by immunofluorescence. Testes showed high gene expression of FADS2, ELOVL2 and ELOVL5 and low expression of FADS1. Intermediate metabolites, enzymes and final products were differently found in Leydig, Sertoli and germinal cells. FADS2 was localized in interstitial cells and elongated spermatids; ELOVL5 in meiotic cells; FADS1 was evident in interstitial tissue, Sertoli cells and elongated spermatids; ELOVL2 in interstitial cells. Epididymal vesicles were positive for FADS1, ELOVL2 and ELOVL5 as well as docosahexaenoic, eicosapentaenoic, and arachidonic acids. This knowledge of fatty acids (FA) metabolism in spermatogenesis and the influence of diet on FA profile could help identify causes of male infertility, suggesting new personalized therapy.

The Special Issue \"Antioxidants in Male Human and Animal Reproduction: In Vitro and In Vivo Studies\", published by Antioxidants and led by us (https://www [...].The Special Issue \"Antioxidants in Male Human and Animal Reproduction: In Vitro and In Vivo Studies\", published by Antioxidants and led by us (https://www [...].

In this review, the role of fatty acids (FA) in human pathological conditions, infertility in particular, was considered. FA and FA-derived metabolites modulate cell membrane composition, membrane lipid microdomains and cell signaling. Moreover, such molecules are involved in cell death, immunological responses and inflammatory processes. Human health and several pathological conditions are specifically associated with both dietary and cell membrane lipid profiles. The role of FA metabolism in human sperm and spermatogenesis has recently been investigated. Cumulative findings indicate F2 isoprostanes (oxygenated products from arachidonic acid metabolism) and resolvins (lipid mediators of resolution of inflammation) as promising biomarkers for the evaluation of semen and follicular fluid quality. Advanced knowledge in this field could lead to new scenarios in the treatment of infertility.

30 percent of infertile men are diagnosed with idiopathic infertility. This study aimed to assess oxidative stress in the semen of 77 patients with idiopathic infertility by measuring F2-isoprostane (F2-IsoP), resolvin D1 (RvD1) levels, and semen parameters. The presence and localization of 8-IsoProstaglandin F2α were determined using immunofluorescence. No significant correlations were observed for F2-IsoP and RvD1 levels with the semen variables. Based on F2-IsoP levels, individuals were classified into two groups: Group 1 (F2-IsoPs ≤ 29.96 ng/mL, 51%) and Group 2 (F2-IsoPs > 29.96 ng/mL, 49%). In comparison to Group 1, Group 2 showed significantly higher F2-IsoP levels (13.33 ng/mL vs. 44.80 ng/mL; p < 0.05), a lower progressive motility percentage (30% vs. 25%; p < 0.05), and increased RvD1 levels (36.09% vs. 44.94%). Immunofluorescence analysis revealed a different localization of 8-IsoProstaglandin F2α in the ejaculated sperm of Group 1 compared to that observed in Group 2. A weak signal was detected in the sperm tail (Group 1, 79.1% vs. Group 2, 36.9; p < 0.01). In spermatozoa of Group 2 patients, a strong signal in the acrosome, midpiece, and tail was highlighted. These findings suggest the need to test oxidative stress during routine semen analysis in patients with idiopathic infertility to improve diagnosis and treatment.

Apelin and other novel adipokines have been associated with normal and pathological reproductive conditions in humans and animals. In this paper, we used a rabbit model to investigate if apelin and resolvin (RvD1) in testis and sperm are associated with the oxidative status of semen and serum testosterone of rabbits fed different diets enriched with flaxseed (alpha-linolenic acid, ALA) or with fish oil (eicosapentaenoic acid, EPA, docosapentaenoic acid, DPAn-3, and docosahexaenoic acid, DHA). Apelin and RvD1 were detected by ELISA and apelin and the apelin receptor by immunofluorescence. Increased levels of apelin in testes from both enriched diets were shown, particularly in the interstitial tissue of the FLAX group. The FLAX diet enhanced serum testosterone, and both enriched diets showed higher levels of malondialdehyde and RvD1 in the testis. In ejaculated sperm, apelin and its receptor were localized in the entire tail of the control and both treated groups. The ryanodine receptor was investigated in rabbit testis; the fluorescent signal was increased in mature elongated spermatids of the FLAX group. In conclusion, this data seems to indicate that FLAX increases the amount of apelin in testis, suggesting an involvement of this adipokine in male reproduction and probably a role in the resolution of the inflammatory status.

F4-Neuroprostanes (F4-NeuroPs), oxidative metabolites of docosahexaenoic acid, act as bioactive lipid mediators enhancing sperm motility and induce capacitation-like changes in vitro. Their biological action is proposed to involve sperm ion channels, in particular ryanodine receptors (RyRs), which regulate intracellular calcium homeostasis. We evaluated the effects of dantrolene, a RyR inhibitor, on motility and vitality of a selected spermatozoa at different concentrations (10, 30, 50, 100 μM). Then sperm motility, acrosome integrity, and RyR localization following co-incubation with dantrolene (D50 or D100 μM) and 4-/10-F4t-NeuroPs (7 ng) were investigated. Acrosomal status was assessed using Pisum sativum agglutinin (PSA) staining and RyR localization by immunofluorescence. D50 was identified as the minimum effective dose to induce significant reductions in sperm motility. F4-NeuroPs significantly increased rapid progressive motility versus controls. Co-incubation with F4-NeuroPs + D50 reduced rapid motility and increased in situ and circular movement. The acrosome staining appeared altered or absent to different percentages, and RyR localization was also seen in the midpiece. These findings suggested that F4-NeuroPs enhance sperm motility via RyR-mediated pathways, as confirmed by dantrolene inhibition. Accordingly, our results underscore the physiological relevance of RyRs in sperm function and suggest new insights into lipid-based mechanisms regulating sperm motility.

This study evaluated the effects of chlorogenic acid (CGA) on human semen and on oxidative stress (OS) induced in vitro in human spermatozoa. After the treatment of the basal semen with 100 µM CGA, rapid and slow sperm progressive motility were evaluated and seminal F2-Isoprostanes (F2-IsoPs), a marker of OS, were quantified by ELISA. In a second set of experiments, semen was treated with 100 µM CGA, 1 mM H2O2 to induce OS, or H2O2+CGA; untreated samples were used as controls. Then, sperm motility, DNA integrity by the acridine orange test, F2-IsoPs and Nrf2 mRNA expression by RT-PCR were quantified. In CGA-treated specimens, rapid progressive sperm motility was increased (p < 0.01) and F2-IsoP levels decreased (p < 0.001) versus controls. The increase of F2-IsoP levels and DNA damage and the decrease of sperm motility after H2O2 treatment was reversed in the presence of CGA, which upregulated Nrf2 mRNA expression. These findings contributed to clarifying CGA’s antioxidant activity and highlighted the positive impact of CGA on sperm progressive motility, suggesting also a possible mechanism of action based on the Nrf2 pathway. CGA can be useful during human semen handling procedures in the laboratory and in optimizing the recovery of motile spermatozoa through selection techniques during assisted reproductive technology protocols.

Spermatozoa are highly differentiated cells that produce reactive oxygen species (ROS) due to aerobic metabolism. Below a certain threshold, ROS are important in signal transduction pathways and cellular physiological processes, whereas ROS overproduction damages spermatozoa. Sperm manipulation and preparation protocols during assisted reproductive procedures—for example, cryopreservation—can result in excessive ROS production, exposing these cells to oxidative damage. Thus, antioxidants are a relevant topic in sperm quality. This narrative review focuses on human spermatozoa as an in vitro model to study which antioxidants can be used to supplement media. The review comprises a brief presentation of the human sperm structure, a general overview of the main items of reduction–oxidation homeostasis and the ambivalent relationship between spermatozoa and ROS. The main body of the paper deals with studies in which human sperm have been used as an in vitro model to test antioxidant compounds, including natural extracts. The presence and the synergic effects of different antioxidant molecules could potentially lead to more effective products in vitro and, in the future, in vivo.

Infertility represents a significant global health challenge, affecting more than 12% of couples worldwide, and most cases of infertility are caused by male factors. Several pathological pathways are implicated in male infertility. The main mechanisms involved are driven by the loss of reduction–oxidation (redox) homeostasis and the resulting oxidative damage as well as the chronic inflammatory process. Increased or severe oxidative stress leads to sperm plasma membrane and DNA oxidative damage, dysregulated RNA processing, and telomere destruction. The signaling pathways of these molecular events are also regulated by Nuclear factor-E2-related factor 2 (Nrf2). The causes of male infertility, the role of oxidative stress in male infertility and the Keap1-Nrf2 antioxidant pathway are reviewed. This review highlights the regulatory role of Nrf2 in the balance between oxidants and antioxidants as relevant mechanisms to male fertility. Nrf2 is involved in the regulation of spermatogenesis and sperm quality. Establishing a link between Nrf2 signaling pathways and the regulation of male fertility provides the basis for molecular modulation of inflammatory processes, reactive oxygen species generation, and the antioxidant molecular network, including the Nrf2-regulated antioxidant response, to improve male reproductive outcomes.